Aseptic processing or manufacturing refers to procedures and activities for preparing drug formulations, filling them into relevant containers such as vials, and finally packaging the products while ensuring the product and production environment remain sterile and contamination free.
Specifically, aseptic filling refers to packaging commercially sterilized products into pre-sterilized containers under sterile conditions to ensure a contamination-free and shelf-stable product. Aseptic filling is also referred to as fill-finish manufacturing.
The main aim of aseptic processing is to prevent the final product from collecting microbes or pyrogens.
Procedures in Aseptic Processing
Aseptic processing comprises lengthy sterilization processes that aim to promote an aseptic environment throughout. Four methods are commonly used to pre-sterilize containers:
- Dry heat sterilization. Containers sensitive to moisture or steam are exposed to high heat for a relevant duration to ensure sterility. Dry heat is also used to depyrogenate the containers. Glass containers are commonly subjected to dry heat sterilization.
- Autoclaving. Containers are placed in an autoclave and subjected to high-pressure steam to kill microbes.
- Radiation sterilization. Gamma irradiation or electron beam irradiation is used to damage the DNA of microbes and render them ineffective.
- Chemical sterilization. Here, containers are sterilized with chemical agents, such as hydrogen peroxide, chlorine, etc.
- Filtration. Drug products go through sterilization filters to trap and remove microbes.
The most common containers used for aseptic filling include glass, metal, and plastic, such as PET.
Overall, aseptic processing happens in three steps that ensure the sterility of products and the environment, as seen below.
- Sterilization of raw products and containers separately
- Packaging the product into pre-sterilized containers
- Ensuring there are no present microbes in the environment that can impact the integrity of products before final sealing and packaging through environmental monitoring and finished product testing.
Is There a Difference Between Aseptic Filling and Sterile Filling?
Although aseptic and sterile filling are used interchangeably on product labels, they have some differences.
Sterile filling and aseptic filling undergo different microbial prevention processes. The sterile fill/finish process is about sterilizing the drug formulations, containers, and production environment to kill microorganisms. On the other hand, aseptic filling processes comprise the techniques and behaviors that maintain the sterility of the production environment, drug formulations, and containers.
What Types of Products Need Aseptic Processing and Why?
Any parenteral products and some implantable devices are the most common candidates for aseptic processing.
Parenteral products are drugs implanted or injected directly through the skin to enable direct administration into tissue organs, blood vessels, or lesions. Examples include eye drops, nasal sprays, ear drops, and most vaccines. Essentially any drug administered through a route other than the digestive tract.
Since such products are filled into vials, pre-filled syringes, or ampules, the containers must be pre-sterilized to deter the presence or reproduction of microbes, hence aseptic processing.
If these products are not processed aseptically, it could encourage contamination. Unfortunately, since they are directly injected into delicate membranes, contaminated products can severely affect the end user.
Generally, the products mentioned below require aseptic processing:
- Biologics: vaccines, monoclonal antibodies, and other biopharmaceuticals
- Ophthalmic products: eye drops and eye ointments
- Parenteral nutrition products: (if administered intravenously for provision of essential nutrients to patients)
- Liquid injectables: vaccines, antibiotics, and other liquid medications
- Sterile powders: antibiotics or powders for reconstitution
Why Is Aseptic Processing So Challenging?
Aseptic processing is quite challenging because it requires complex engineering of operations to prevent the contamination of products. Let’s explore these challenges further.
Risks of Contamination
Aseptic processing relies on detailed procedures, high-level controls, and specialized equipment to guarantee the safety of products.
Because of the high degree of care and meticulous control required, aseptic processing poses more risks. Any slip-up that allows contamination into products or the production environment can lead to impacts such as:
- Loss of valuable products. Contamination of products can render them ineffective and cause devastating losses for a company. If the contamination is not caught before dispatch to consumers, it will lead to product recalls. This leads to lost trust from your customers.
- Potential health risks. Failure to maintain an aseptic environment throughout the process could cause harmful health risks to consumers after using a contaminated product. For example, in 2020, the FDA announced that some drugs were contaminated with a ‘potential human carcinogen known as NMDA.’ This occurred because there was a lack of controls to maintain an aseptic environment.
- Production delays. Stringent regulations governing aseptic manufacturing mean that there will be prolonged delays should a product be exposed to microbial contamination.
Fortunately, even though maintaining an aseptic environment is challenging, you can achieve it with the right equipment and controls.
Maintaining an Aseptic Environment
Organizations should see aseptic processing as a culture rather than just an operation to maintain the proper aseptic processes.
Personnel need to understand the why and the consequences if the why is forgotten. In addition, companies should introduce stringent comprehensive risk assessments at every step of aseptic processing. Maintaining an aseptic environment requires more than the mandated testing. Companies should invest significantly in intentionally-designed controls that validate and qualify the aseptic process.
These controls should cut across the following variables:
- Facility design; HEPA filters, airlocks, room classifications, etc.
- Building management; monitoring air flow movement, temperature, humidity, pressure, etc.
- Procedures and personnel; equipment flow, cleaning, pre-sterilization techniques, gowning, etc.
Regulatory Compliance
In addition to the mentioned challenges, companies that perform aseptic manufacturing MUST conform to strict standards and regulations governed by the Food and Drug Administration (FDA).
Specifically, companies must accurately define and implement process monitoring criteria and safeguards. These standards minimize contamination of products and the production environment.
They also help identify contamination early so relevant mitigations can be implemented. Finally, these standards enable the generation of data for referencing and auditing aseptic manufacturing.
Adhering to these regulations and standards takes time and lots of effort. That’s why most companies in pharmaceutical-related sectors choose to work with contract manufacturing companies (CMOs). These companies provide services such as aseptic filling of injectable drugs.
Aseptic filling services help pharmaceutical companies, such as yours, to provide contamination-free and effective products to your clientele.
Learn more about Afton Scientific’s aseptic filling services.